The objective of our proposed research is to extend our ongoing studies of suppressor cell activity in tumor-draining lymph nodes as a possible immunologic escape mechanism in bladder cancer patients. To this end, we will test mononuclear cells from tumor-draining lymph nodes for: 1. spontaneous suppressor activity in an antibody-dependent cell-mediated cytotoxicity (ADCC) model system, 2. spontaneous suppressive effects on the in vitro generation of cytotoxic T cells against 253J human bladder cancer cells in mixed lymphocyte-tumor cell culture, and 3. the nonspecific induction of suppressor cells from precursor cells by concanavalin A (Con A). We will also correlate spontaneous suppressor cell activity with Con A-inducible suppressor cell function. We intend to determine the nature of the suppressor cells by performing our assays with purified effector cell subpopulations. We will also continue our studies on the isolation, quantification, and characterization of cell-free suppressor extracts derived from suppressor cell populations. We will perform experiments using suppressor cells and extracts in both the autologous and allogenic situations to determine whether there are genetic restrictions on the expression of supprssor cell functions in humans. We will study our patients sequentially to determine what effects tumor stage, progression, and treatment have on suppressor cell activity.